In the field of nucleic acid therapy, virus vectors and synthetic carriers (non-viral carriers) have thus far been examined as a carrier for delivering nucleic acids to target cells or a target tissue.
Like drug deliver systems (DDS) that have been examined in the conventional therapy, synthetic carriers involve risks of, e.g., toxicity. Nevertheless, compared to virus vectors, they are considered to be less toxic, have less restriction on the size of nucleic acids to be carried, and allow for more accurate molecular design. Therefore, intense research and development have been made on synthetic carriers.
Typical synthetic carriers include cationic lipids and cationic polymers, which can form an ion complex with DNA, which is negatively charged.
With regard to cationic lipids (e.g., lipofectin), certain positive results have been obtained in vitro (see, e.g., Non-Patent Document 1), although desired results have not necessarily been achieved in vivo.
With regard to cationic polymers, various polymers have been studied, such as poly(L-lysine), DEAE-dextran, polyethyleneimine (see, e.g., Non-Patent Document 2), and chitosan (see, e.g., Non-Patent Document 3). However, these cationic polymers not only have cytotoxicity, but are also insufficient either in nucleic acid introduction efficiency or in gene expression efficiency.
The present inventors have reported that self-assembly of a block copolymer which has a cationic polymer segment containing amine groups on its side chains and an uncharged hydrophilic polymer segment such as polyethylene glycol (PEG) a polyion complex (PIC) yields a polymeric micelle encapsulating a nucleic acid, which exhibits reduced cytotoxicity and shows a certain level of nucleic acid introduction efficiency and gene expression efficiency (see Patent Document 1: JP2004-352972A). However, nucleic acid deliver system using such a PIC polymeric micelle still has room for improvement in nucleic acid introduction efficiency and gene expression efficiency.
The present inventors have also reported that a cationic homopolymer, which contains certain amine groups on its side chains, can be mixed with a nucleic acid to markedly improve nucleic acid introduction efficiency and gene expression efficiency while relatively reducing toxicity on animal cells (especially on mammalian cells) (Patent Document 2: WO2006/085664A). However, nucleic acid deliver system using such a homopolymer still has room for improvement in reduction in cytotoxicity.